Variations in Practice and Geographic Disparities Between Dedicated Multidisciplinary Clinics for BRCA1/BRCA2 Mutation Carriers in Israel.

BACKGROUND: Population screening for the BRCA mutations in Ashkenazi Jewish women was recently implemented in Israel and is expected to lead to a 10-fold increase in the diagnosis of asymptomatic carriers. Performing the screening follow-up within multidisciplinary dedicated clinics for carriers is recommended for early detection and risk reduction. OBJECTIVES: : To determine the availability, capacity, and practices of dedicated screening clinic for BRCA carriers in Israel. METHODS: A telephone-based survey of all public hospitals in Israel was conducted October 2020 to August 2021 to determine whether they had a dedicated clinic. Dedicated clinics were defined as multidisciplinary screening clinics offering at least breast and gynecological screening and risk reducing services on site. The clinic director or nurse navigator answered a questionnaire about screening practices followed by a semi-structured interview. RESULTS: Of the ten dedicated BRCA clinics found in Israel, nine participated. Approximately 4500 BRCA carriers are currently being followed. No specialized clinics are available in the southern district or in the northernmost half of the northern district of Israel, leading to a disparity between periphery and center. Screening recommendations, although asserted as adhering to international guidelines, vary among clinics including age at initiating of clinical exam, use of adjunct imaging modalities, and follow-up during lactation and after risk reducing surgery. CONCLUSIONS: There is a suboptimal distribution of dedicated clinics for BRCA carriers in Israel. Nationally centralized attempt to create guidelines that will unify screening practices is warranted, especially considering the expected increase in demand.

Personalized Screening for Breast Cancer: Rationale, Present Practices, and Future Directions.

Ever since screening for early breast cancer (BC) diagnosis was shown to decrease mortality from the disease, screening programs have been widely implemented throughout the world. Targeted age groups and schedules vary between countries but the majority use a population-based approach, regardless of personal BC risk. The purpose of this review was to describe current population-based screening practices, point out some of the shortcomings of these practices, describe BC risk factors and risk assessment models, and present ongoing clinical trials of personalized risk-adapted BC screening. Three ongoing, large-scale, randomized controlled clinical trials (WISDOM in the US, MyPEBS in Europe, and TBST in Italy) were identified through a search of the MEDLINE and US National Library of Medicine (ClinicalTrials.gov) databases. In these trials, women either undergo standard or personalized screening. The trials vary in methods of risk stratification and screening modalities, but all aim to examine whether personalized risk-adapted screening can safely replace the current population-based approach and lead to rates of advanced-stage BC at diagnosis comparable with those of current screening regimens. The results of these trials may change current population-based screening practices.

Diffusivity in breast malignancies analyzed for b > 1000 s/mm2 at 1 mm in-plane resolutions: Insight from Gaussian and non-Gaussian behaviors.

Diffusion-weighted imaging (DWI) can improve breast cancer characterizations, but often suffers from low image quality -particularly at informative b > 1000 s/mm2 values. The aim of this study was to evaluate multishot approaches characterizing Gaussian and non-Gaussian diffusivities in breast cancer. This was a prospective study, in which 15 subjects, including 13 patients with biopsy-confirmed breast cancers, were enrolled. DWI was acquired at 3 T using echo planar imaging (EPI) with and without zoomed excitations, readout-segmented EPI (RESOLVE), and spatiotemporal encoding (SPEN); dynamic contrast-enhanced (DCE) data were collected using three-dimensional gradient-echo T1 weighting; anatomies were evaluated with T2 -weighted two-dimensional turbo spin-echo. Congruence between malignancies delineated by DCE was assessed against high-resolution DWI scans with b-values in the 0-1800 s/mm2 range, as well as against apparent diffusion coefficient (ADC) and kurtosis maps. Data were evaluated by independent magnetic resonance scientists with 3-20 years of experience, and radiologists with 6 and 20 years of experience in breast MRI. Malignancies were assessed from ADC and kurtosis maps, using paired t tests after confirming that these values had a Gaussian distribution. Agreements between DWI and DCE datasets were also evaluated using Sorensen-Dice similarity coefficients. Cancerous and normal tissues were clearly separable by ADCs: by SPEN their average values were (1.03 ± 0.17) × 10-3 and (1.69 ± 0.19) × 10-3  mm2 /s (p < 0.0001); by RESOLVE these values were (1.16 ± 0.16) × 10-3 and (1.52 ± 0.14) × 10-3 (p = 0.00026). Kurtosis also distinguished lesions (K = 0.64 ± 0.15) from normal tissues (K = 0.45 ± 0.05), but only when measured by SPEN (p = 0.0008). The best statistical agreement with DCE-highlighted regions arose for SPEN-based DWIs recorded with b = 1800 s/mm2 (Sorensen-Dice coefficient = 0.67); DWI data recorded with b = 850 and 1200 s/mm2 , led to lower coefficients. Both ADC and kurtosis maps highlighted the breast malignancies, with ADCs providing a more significant separation. The most promising alternative for contrast-free delineations of the cancerous lesions arose from b = 1800 s/mm2 DWI. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3.

Diagnostic yield of multigene panel testing in an Israeli cohort: enrichment of low-penetrance variants.

BACKGROUND: Carriers of pathogenic variants (PVs) in moderate-high-penetrance cancer susceptibility genes are offered tailored surveillance schemes for early cancer diagnosis. The clinical implications of low-penetrance variant carriers are less clear. METHODS: Clinical and demographic data were retrieved for a cohort of Israeli individuals who underwent oncogenetic testing by the 30-gene cancer panel at Color Genomics laboratory, between 04/2013 and 12/2018. RESULTS: Of 758 genotyped individuals, 504 had been diagnosed with cancer prior to testing: 283 (56%) had breast cancer and 106 (21%) colorectal cancer. Pathogenic or likely pathogenic (P/LP) variants were detected in 123 (16%) individuals. Overall, 44 different P/LP variants were detected in 18/30 cancer susceptibility genes; 20 of them were founder/recurrent mutations. Of the carriers, 39 (32%), 10 (8%), and 74 (60%) carried high-, moderate-, or low-penetrance variants, respectively. After excluding low-penetrance variants, 7% (33/504) of all cancer patients, 6% of breast or ovarian cancer patients were found to be carriers, as well as 7% (14/203) of individuals with colonic polyps, and 4% (11/254) of cancer-free individuals. CONCLUSIONS: The diagnostic yield of moderate- and high-penetrance PVs using multigene panel testing was 6%, with 3.7% carriers of non-recurrent PVs. This yield should be discussed during pre-test counseling, and emphasizes the need for harmonized recommendations regarding clinical implications of low-penetrance variants.

Trans-Vertical Mastectomy With Immediate Implant-Based Reconstruction: A Retrospective, Observational Study.

BACKGROUND: In women with large and ptotic breasts who require a mastectomy and immediate, implant-based reconstruction, long flaps pose a high risk for flap ischemia and necrosis. A new trans-vertical incision for skin-reducing mastectomy is described, which reduces the skin envelope and lifts the breast. OBJECTIVES: The authors sought to describe the new mastectomy access incision and assess its efficacy and safety when followed by immediate implant-based reconstruction. METHODS: This retrospective analysis included 70 consecutive patients (101 breasts) with large and ptotic breasts who underwent a unilateral (n = 39; 55.7%) or bilateral (n = 31; 44.3%), skin-reducing mastectomy utilizing the trans-vertical approach for either breast cancer or risk reduction. All received immediate one- (n = 86; 85.5%) or two-stage (n = 15; 14.5%), implant-based reconstruction utilizing acellular dermal matrix. RESULTS: Mean age was 50.1 years and mean body mass index was 25.6 kg/m2. After a median follow-up of 4.9 years, the number of breasts with minor and major complications was 21 (20.8%) and 26 (25.7%), respectively. The most common major complications were skin-flap necrosis (n = 12; 11.9%) and infection (n = 8; 7.9%). All occurred within 3 months postsurgically. There were 7 cases of capsular contracture (6.9%) and 5 reconstruction failures (5.0%). Higher body mass index (P < 0.01) and breast weight (P < 0.05) were associated with increased complication rates. According to BREAST-Q, 55/64 patients (85.9%) were somewhat or very satisfied with the aesthetic outcome. CONCLUSIONS: The trans-vertical approach is an effective, reproducible, and safe alternative to conventional skin-reducing mastectomy, with favorable aesthetic outcomes, in patients with large and ptotic breasts.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Postoperative Complications Following Lumpectomy With Intraoperative X-Ray Radiation Therapy: A Retrospective Comparative Study.

BACKGROUND: Lumpectomy with intraoperative radiation (IORT) is a relatively new modality for the treatment of early breast cancer. IORT delivers targeted radiation to the tumor bed and obviates the need for external beam radiation (EBRT) in 85% of the cases. IORT is being used increasingly around the world, however information regarding early and late postoperative complications associated with the procedure is limited. AIM: To describe and compare complication rates after lumpectomy and IORT with those seen after lumpectomy and EBRT or lumpectomy alone. METHODS: Clinical, demographic, and histopathological data were collected from electronic medical records and a retrospectively maintained database. Postoperative complications were compared for patients undergoing lumpectomy with IORT, lumpectomy with EBRT, and lumpectomy alone over the same period. RESULTS: A total of 445 patients were included in the study: 113 underwent lumpectomy with IORT, 253 had lumpectomy followed by EBRT, and 79 had Lumpectomy alone. Postoperative seroma was documented in 74 patients (65%) after IORT,87 (34%) after EBRT, and 9 (11%) after lumpectomy alone (P = .000). Surgical site infection requiring antibiotic treatment was diagnosed in 26 patients (23%) after IORT, 38 (15%) after EBRT, and 5 (6%) after lumpectomy alone (P = .013). Postoperative erythema was documented in 39 patients (34%) after IORT, 40 (16%) after EBRT, and 5 (6%) after lumpectomy alone (P = .000). Postoperative minor complications such as scar and breast deformity, edema, Mondor's syndrome, and chronic tenderness, were documented in 62 patients (55%) after IORT, 119 (47%) after EBRT, and 13 (17%) after lumpectomy alone (P = .000). The average follow-up was 14 months. CONCLUSIONS: IORT is associated with an increased rate of postoperative complications compared to EBRT or lumpectomy alone. Most complications are minor and transient. We hypothesize that the increased occurrence of complications may also be attributed to overreporting, which is associated with the introduction of a new technology. Educating physicians and patients about potential complications and their course may help establish expectations and improve the management of postoperative complications.

Screening Mammography for Males With Elevated Breast Cancer Risk, Mutation Carriers, and Gynecomastia.

INTRODUCTION: The recommendations for annual mammography for male carriers with gynecomastia are controversial. This study investigated the potential link between gynecomastia and breast cancer in male carriers. PATIENTS AND METHODS: The database of a tertiary medical center was retrospectively searched for all male patients who underwent at least 1 digital mammography study from 2016 to 2023. Known carriers of a pathogenic variant in a high-risk breast-cancer gene were identified. Patients were stratified by carrier status, diagnosis of breast cancer, and diagnosis of gynecomastia. Data on demographics, hormone profile, and pathology results were compared. RESULTS: The cohort included 446 men of whom 82 were known carriers. Gynecomastia was diagnosed by mammography in 251 patients: 239/364 noncarriers (66%) and 12/82 carriers (15%) (P < .0001). Breast cancer was found in 21/364 noncarriers (6%) and 6/82 carriers (7%) (P < .6), and in 10/251 patients with gynecomastia (4%) and 17/193 (9%) without gynecomastia (P < .05). Among patients without gynecomastia, the number of breast cancer cases was similar in carriers and noncarriers (P = .3). Among patients with gynecomastia, the rate of breast cancer was higher in carriers (P < .08). On logistic regression analysis, the effect of gynecomastia on carriers was significant (P = .02). The odds ratio for a breast cancer diagnosis was 5.8 in the presence of gynecomastia (95% CI, 1.1-31, P < .04) and 0.52 in the absence of gynecomastia (95% CI, 0.2-1.7, P < .3). CONCLUSION: Gynecomastia may be associated with an increased risk of breast cancer in carriers. Larger studies are needed to determine whether and when to screen male carriers.

Tumor STAT3 tyrosine phosphorylation status, as a predictor of benefit from adjuvant chemotherapy for breast cancer.

Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signaling pathways. In breast cancer cell lines and xenograft models activated STAT3 participates in breast tumorigenesis, while studies in humans have demonstrated that phosphorylated (tyrosine705)-STAT3 is a marker of good prognosis in breast cancer. In order to resolve this paradox we hypothesized that in clinic, phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy; therefore the goal of this study was to determine the usefulness of phospho-STAT3 status as a predictor of benefit from adjuvant chemotherapy in breast cancer patients. Immunohistochemical analysis of phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of phospho-STAT3 was retrospectively correlated with pathological parameters and overall survival in patients who were or were not treated with adjuvant chemotherapy. Of 375 tissue specimens interpretable for phospho-STAT3, 134 (36 %) exhibited positive phospho-STAT3 nuclear expression. Among 234 patients who received adjuvant therapy, those with tumors displaying positive phospho-STAT3 nuclear expression had a better ten-year rate of overall survival than patients with tumors displaying negative phospho-STAT3 nuclear expression (P = 0.001). Among patients who did not received adjuvant chemotherapy, positive phospho-STAT3 nuclear status was not correlated with increased overall survival (P = 0.54). Positive phospho-STAT3 was correlated with improved overall survival only among patients who received adjuvant chemotherapy in a multivariate analysis adjusted for stage, grade, hormonal status, Her2 status, and age, irrespective of the chemotherapy regimen received (hazard ratio for death, 0.35 [95 % CI 0.188-0.667]; P = 0.001). These findings support the role of phospho-STAT3 as a marker of favorable outcome in breast cancer patients treated with adjuvant chemotherapy. Whether phospho-STAT3 has a predictive role of benefit from adjuvant chemotherapy has to be validated on prospective, randomized, controlled studies.

A novel functional infrared imaging system coupled with multiparametric computerised analysis for risk assessment of breast cancer.

OBJECTIVE: We evaluated a functional three-dimensional (3D) infrared imaging system (3DIRI) coupled with multiparametric computer analysis for risk assessment of breast cancer. The technique provides objective risk assessment for the presence of a malignant tumour based on automated parameters derived from a clinically known training set. METHODS: Following institutional review board approval, we recruited 434 women for this prospective multicentre trial, including 256 healthy woman undergoing routine screening mammography with BI-RADS-1 results and 178 women with newly diagnosed breast cancer. This was a two-phase study: an initial training and calibration phase, followed by a two-armed blinded evaluation phase (52 healthy and 66 with breast cancer). 3DIRI data sets were acquired using a non-contact, no radiation system. RESULTS: The sensitivity and specificity of functional infrared imaging in providing the correct risk for the presence of breast cancer were 90.9 % and 72.5 %, respectively. The area under the ROC curve was 86 %. Forty-two of the 60 (70 %) cancers in women correctly classified by the system as suspicious were smaller than 20 mm in size. CONCLUSION: The preliminary blinded results of this novel technology show sufficient performance of functional infrared imaging in providing risk assessment for breast cancer to warrant further clinical studies. KEY POINTS: • 3D functional infrared imaging (3DIRI) provides new metabolic signatures from breast lesions. • 3DIRI offers high sensitivity for risk assessment of breast cancer. • It also has reasonable specificity. • This initial experience warrants further evaluation in larger clinical trials.

Association between patient age, volume of breast tissue excised, and local recurrence.

INTRODUCTION: Young breast cancer patients undergoing breast-conserving surgery have a significantly higher rate of local recurrence compared with older women. The aim of this study was to assess whether the volume of tissue excised may be associated with the higher local recurrence rate seen in young patients. METHODS: Medical records of patients who underwent breast-conserving surgery at a single institution between 1987 and 2001 were reviewed retrospectively. Tumor and specimen volumes were extracted from pathology reports, and specimen-to-tumor-volume ratio (STVR) was calculated. STVR and local recurrence rates were compared for women under 40 and over 50 y of age. RESULTS: Data were available for 97 patients under age 40 and 150 women over age 50. Patients under 40 had significantly more high-grade tumors (57% versus 25%, P < 0.0005). There was no significant difference in average tumor size; however, both specimen volume and STVR (log scale) were lower in younger women: 4.63 versus 5.20, P < 0.001 and 3.81 versus 4.55, P < 0.001, respectively. Younger women also had a significantly higher rate of local recurrence: 17% versus 7%, P = 0.03. On multivariate analysis, lower STVR was significantly associated with a higher recurrence rate for the entire group (P < 0.005) and, to a lesser degree, in younger women (P = 0.05). CONCLUSIONS: The volume of tissue removed in women younger than 40 undergoing breast-conserving therapy tends to be smaller than in older women. This may contribute to the higher local recurrence rates observed in young breast cancer patients.

Surgical site infection in reconstructive and aesthetic breast surgery: A single center retrospective analysis of the association between healthcare workers and infections.

BACKGROUND: Reconstructive and aesthetic breast surgeries are frequently performed procedures, and the consequences of a postoperative infection are devastating both for the patient and the healthcare (HC) system. Over the years, there has been heightened interest in the physical and mental well-being of physicians and HC workers. Little is known about the relationship between HC workers and surgical site infections (SSI), and whether HC workers are at an increased risk for SSI. The aim of this study was to investigate whether women working in the HC system have an increased risk for SSI following reconstructive and aesthetic breast surgery. MATERIALS AND METHODS: We conducted a retrospective analysis of all patients who underwent aesthetic and reconstructive breast surgery at our institution between the years 2013-2020. Women who were recognized as HC workers were analyzed in a separate group and compared to those who were not. RESULTS: Records of 378 patients were reviewed, of whom 53 (14%) were identified as HC workers. The overall infection rate was 17.4%. HC workers manifested a higher infection rate than the other group (32% vs. 15.1%, p<0.05) and a significantly higher relative risk for SSI (RR 2.12, p<0.01). CONCLUSIONS: Women working in the HC system may have an increased risk of developing postoperative infectious complications following aesthetic and reconstructive breast-related surgery. Further research is needed to corroborate these findings and elucidate the causes.

Thyroid Hormones and Morphological Features of Primary Breast Cancer.

BACKGROUND/AIM: Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC. RESULTS: We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level >5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027). CONCLUSION: The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis.

Potential Refinement of Recurrence Score by pSTAT3 Status.

The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.

MRI background parenchymal enhancement in patients with invasive lobular carcinoma: Endocrine hormonal treatment effect.

OBJECTIVES: High background parenchymal enhancement (BPE) levels and asymmetric distribution could cause diagnostic uncertainty due to morphological similarity to breast cancer, especially invasive lobular carcinoma (ILC). We investigated BPE in ILC patients, its association with the tumor hormonal profile, and the effect of endocrine treatment (ET). METHODS: The analysis included all MRI examinations performed at our institution between 2010 and 2019 for ILC-diagnosed patients. Baseline study and the first follow-up study were reviewed. Digital medical records were reviewed to retrieve demographics/pathology results/treatment information. BPE and fibroglandular tissue were assessed qualitatively on the contralateral breast according to the criteria of the Breast Imaging Reporting and Data System (BI-RADS). RESULTS: The study included 129 patients. Most (91%) had pure ILC. All received ET; 12% also received chemotherapy; 90% had surgery first; 70% by breast conservation. On the baseline MRI, 70% had mild or moderate BPE; whereas, on the follow-up study, the majority (59%) had minimal BPE. Most BPE reductions were by 2 degrees. In the baseline study, additional biopsies were required in 59% of cases, and in 17%, a short-term follow-up was recommended. In the follow-up study, biopsies were recommended in 10%, and a short-term follow-up was requested in 16%. A correlation between progesterone receptor intensity index and baseline BPE level was observed (r = 0.3, p = 0.004). CONCLUSION: ILC patients usually exhibit high BPE. ET decreases BPE, and therefore may decrease false-positive interpretations. Additional research is needed to explore whether study can be performed on ET without compromising sensitivity. KEY POINTS: ∙ High background parenchymal enhancement levels reduces breast MRI sensitivity, yielding high false positive rates especially when reporting cases of invasive lobular carcinoma [ILC].∙Treatment of ILC with endocrine therapy reduces background parenchymal enhancement and thus could decrease these false-positive interpretations.

Oncoplastic breast consortium recommendations for mastectomy and whole breast reconstruction in the setting of post-mastectomy radiation therapy.

AIM: Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. METHODS: A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. RESULTS: The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. CONCLUSIONS: The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR.

Innovative Standards in Surgery of the Breast after Neoadjuvant Systemic Therapy.

BACKGROUND: The goal of neoadjuvant systemic therapy (NST) in breast cancer is to downstage tumors and downgrade treatment. Indications are constantly evolving. These changes raise practical questions for planning of surgery after NST. SUMMARY: In this review we discuss current evolving aspects of surgery of the breast after NST. Breast-conserving surgery (BCS) eligibility increases after NST - both neoadjuvant chemotherapy (NAC) and neoadjuvant endocrine therapy. Adequate margin width in NST and upfront surgery are similar - "no tumor on ink" for invasive cancer. Oncoplastic breast surgery after NST is feasible - both for BCS and mastectomy with reconstruction. There is increasing interest in the possibility of omitting surgery in patients with a complete response to NAC. Several trials are being conducted in aim of achieving acceptable prediction of pathological complete response, by combination of imaging and percutaneous biopsy of the tumor bed, as well as assessing the safety of such an approach. KEY MESSAGES: Surgery of the breast after NST should be determined not only according to biologic and anatomic parameters at diagnosis, but is dynamic, and must be tailored according to the response to therapy. The omission of surgery in exceptional responders after NAC is being explored.